Critical gaps in our understanding include whether folliculotropic, syringotropic, or other MF variants respond differently to combination therapy; the role of disease stage (patch, plaque, tumor) in determining treatment response; how transformed MF might behave differently, given its altered biology; and the impact of prior therapies on the IL-4/CD30 axis and subsequent response to combination treatment. This evidence concerns the gene TNFRSF8 and mycosis fungoides.